The invention relates to a process for the preparation of an immunoglobulin solution suited for intravenous administration and containing IgM in somewhat concentrated form, wherein an IgM-containing protein fraction obtained by a conventional fractionating process from blood plasma or serum is treated with such amounts of .beta.-propiolactone that the ratio of .beta.-propiolactone to a 5% solution of the IgM-containing proteins is from about 0.05 to 0.15 ml per 100 ml, and is then worked up in known manner.
The IgM-containing immunoglobulin preparation prepared in accordance with the invention and suited for intravenous administration has a high antibody activity against gram-negative and gram-positive bacteria.
While a number of processes for the preparation of intravenously compatible immunoglobulin preparations of the IgG type and containing primarily antibodies against viruses has been developed, such as degradation by means of pepsin (Schultze, H. E., and G. Schwick, Dtsch. med. Wochenschrift 87, 1643 [1962]), degradation by means of plasmin (Barandun, S., et. al., Vox Sang. 28, 157 [1975]), degradation by means of hydrochloric acid (Barandun, S., et. al., Vox Sang. 7, 187 [1962]), or chemical modification by means of .beta.-propiolactone (Stephan, W., Z. Klin. Chem. Klin. Biochem. 7, 282 [1969]), there is as yet no method that would permit the preparation of intravenously compatible, highly purified immunoglobulin preparations containing IgM in the concentrated form required for the control of bacterial infections, although IgM-containing fractions, such as Cohn Fraction III, have been available since the years 1940 to 1950 when alcohol-fractionation techniques were developed. The fact that nonetheless no intravenously compatible IgM concentrates have been made available up to now is probably attributable to the structural differences between the IgM and IgG molecules with respect to the interrelation between anticomplementary activity and intravenous incompatibility.
In the light of the present state of the art, a denaturation due to the fractionating process induces at the Fc site of the antibody molecule a so-called anticomplementary activity, which is responsible for the intravenous incompatibility of fractionated immunoglobulins that have been not been subjected to a special treatment. Since the IgM antibody contains five Fc sites per molecule, in contrast to the IgG antibody which only contains one Fc site per molecule, it was to be expected that the anticomplementary activity of IgM-containing immunoglobulin preparations could be overcome only through a drastic increase in the concentration of the modifiers (enzymes and acylating agents), which, however, would result in a substantial loss of antibody activity, as has been shown by the example of chemical modification of IgG.